The aim of this study was to evaluate the effect of β-caryophyllene on hypercholesterolemia using a model of hyperlipidemia induced by Triton WR-1339 in rats, as well as its possible effect on hepatic antioxidant enzymes. Thus, total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured in serum, while reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), hepatic 3-hydroxy-3-methylglutayl coenzyme A (HMG-CoA) reductase, superoxide dismutase (SOD), and catalase (CAT) activities were measured in the hepatic tissue...

OBJECTIVES: All patients with lower extremity peripheral arterial disease (LE-PAD) should benefit from recommended pharmacologic therapies including antiplatelet agents, angiotensin converting enzyme (ACE) inhibitors or Angiotensin receptor blockers (ARBs), and HMG-CoA-reductase inhibitors (statins). In the present study, this triple therapy was defined as the best medical treatment. This study was designed to determine the number of patients who received best medical treatment at admission and at discharge from a vascular surgery department...

BACKGROUND: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk...

PCSK9 is a protease, synthesized mainly in the liver, which promotes the hepatic degradation of the LDL receptor and consequently decreases LDL receptor density and clearance of LDL particles. Statins inhibit HMG-CoA-reductase activity, an enzyme that catalyses an important step in hepatic cholesterol biosynthesis. The decrease of the hepatic intracellular cholesterol pool produced by these drugs upregulates the activity of the SREBP2 transcription factor, which subsequently stimulates the expression of the LDL receptor gene, an effect that is followed by an increase in the serum concentration of PCSK9...

Tocotrienols accelerate the degradation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase that catalyzes the biosynthesis of mevalonate; the latter is essential for preadipocyte differentiation. Tocotrienols also down-regulate peroxisome proliferator-activated receptor γ (PPARγ), a key regulator of adipocyte differentiation. We hypothesized that mevalonate deprivation and PPARγ down-regulation mediate d-δ-tocotrienol-induced inhibition of adipocyte differentiation. The objectives of this study were to determine the effect of d-δ-tocotrienol on 3T3-F442A preadipocyte differentiation and the involvement of PPARγ and mevalonate...

Chronic subdural haematoma (CSDH) is a common neurosurgical condition. Burr-hole for drainage is an effective treatment. However, recurrence can be up to 8-33% and is associated with morbidities and mortalities. The underlying pathogenesis was postulated to be localised inflammation and pathological aberrant vessels formation. Atorvastatin, an HMG-CoA reductase inhibitor, is a type of lipid-lowering medication. In animal studies and a preliminary clinical trial, Atorvastatin was shown to be effective in the treatment of CSDH...

INTRODUCTION: Anti-3-hydroxy-3-méthylglutaryl-coenzyme A reductase antibody-associated necrotizing autoimmune myopathy has been recently described (2011). This myopathy is distinct from statin toxic myopathy. Our objective is to report on the clinical and para-clinical characteristics of this myopathy and to show the difficulties of therapeutic care. CASE REPORTS: We describe 4 cases of patients followed-up in Brittany, France. All data have been analyzed retrospectively...

Dyslipidemia is a common pathology throughout the industrialized world, and HMG-CoA reductase inhibitors (statins) are often administered to treat elevated lipid levels. Substantial concern has been raised regarding the aggressive clinical lowering of cholesterol, particularly in light of a growing body of research linking low circulating lipid levels with negative behavioral outcomes in both human samples and non-human primate models. In 2009, Goldstein and colleagues tentatively speculated that the greed, impulsiveness, and lack of foresight that lead to the worldwide economic collapse in 2007-2008 could have been caused (in part) by depressed population cholesterol levels resulting from the widespread use of statins by workers in the financial services industry...

This study measured the impact of alisol B 23-acetate and alisol A 24-acetate, the main active ingredients of the traditional Chinese medicine Alismatis rhizoma, on total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C) levels of hyperlipidemic mice. The binding of alisol B 23-acetate and alisol A 24-acetate to the key enzyme involved in the metabolism of TC, 3-hydroxy-3-methylglutary-coenzyme A (HMG-CoA) reductase, was studied using the reagent kit method and the western blotting technique combined with a molecular simulation technique...

In addition to its antioxidant properties, γ-tocotrienol also has the ability to inhibit HMG-CoA reductase, which is the key enzyme in the mevalonate pathway for cholesterol biosynthesis. Statins, the competitive inhibitors of HMG-CoA reductase, display potent anticancer activity and reversal ability of multidrug resistance in a variety of tumor cells, which is believed to be due to their inhibition of HMG-CoA reductase. Here, we determined the role of the mevalonate pathway in γ-tocotrienol-mediated reversal of multidrug resistance in cancer cells...

PURPOSE: Adverse drug reactions (ADRs) including medication allergies are not well-described among large national cohorts. This study described the most common documented medication allergies and their reactions among a national cohort of Veterans Affairs (VA) inpatients. METHODS: We evaluated inpatient admissions in any VA Medical Center from 1 January 2000 to 31 December 2014. Each admission was linked with allergy history preceding or upon admission. Individual drugs were aggregated into drug class category including: penicillins, sulfonamides, angiotensin converting enzyme (ACE) inhibitors, opiates, HMG-CoA reductase inhibitors ("statins") and non-steroidal anti-inflammatory inhibitors (NSAID)...

As part of its Single Technology Appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of evolocumab (Amgen) to submit evidence on the clinical and cost effectiveness of evolocumab. The appraisal assessed evolocumab as monotherapy or in combination with a statin (HMG-CoA reductase inhibitor) with or without ezetimibe, or in combination with ezetimibe (without statin therapy), in adult patients with primary hypercholesterolaemia (which includes mixed dyslipidaemia), for whom statins do not provide optimal control of their low-density lipoprotein cholesterol (LDL-C) levels and/or for whom statins are contraindicated or not tolerated...

HeLa is one of the oldest and most commonly used cell lines in biomedical research. Owing to the ease of which they can be effectively synchronized by various methods, HeLa cells have been used extensively for studying the cell cycle. Here, we describe several protocols for synchronizing HeLa cells from different phases of the cell cycle, including G1 phase using the HMG-CoA reductase inhibitor lovastatin, S phase with a double thymidine block procedure, and G2 phase with the CDK1 inhibitor RO-3306. Cells can also be enriched in mitosis using nocodazole and mechanical shake-off...

We report an in silico method to screen for receptors or pathways that could be targeted to elicit beneficial transcriptional changes in a cellular model of a disease of interest. In our method, we integrate: (1) a dataset of transcriptome responses of a cell line to a panel of drugs; (2) two sets of genes for the disease; and (3) mappings between drugs and the receptors or pathways that they target. We carried out a gene set enrichment analysis (GSEA) test for each of the two gene sets against a list of genes ordered by fold-change in response to a drug in a relevant cell line (HL60), with the overall score for a drug being the difference of the two enrichment scores...

The availability of effective drugs targeting the major risk factors of cardiovascular disease (CVD) has reduced morbidity and mortality. Cumulative relative risk of CVD events can be reduced by 75 % with a combination of aspirin, a β-adrenoceptor antagonist (β-blocker), an HMG-CoA reductase inhibitor (statin), and an angiotensin-converting enzyme inhibitor. The principal pharmacodynamics of these drugs cannot explain the entirety of their cardioprotective action, as other drugs with similar pharmacologic targets have not been associated with favorable clinical effects...

PURPOSE: HMG-CoA reductase inhibitors, also termed statins, are used to reduce the risk of coronary artery disease. Two oxidatively modified low-density lipoprotein (LDL) complexes, serum amyloid A-LDL (SAA-LDL) and α1-antitrypsin-LDL (AT-LDL), serve as atherosclerotic, inflammatory, and cardiovascular risk markers. In this study, we examined the effects of hydrophilic rosuvastatin (RSV) and lipophilic pitavastatin (PTV) on these markers in patients with hypercholesterolemia. METHODS: The present study was a sub-analysis of our previous STAT-LVDF study...

OBJECTIVE: The present study was aimed to investigate the characteristics of simvastatin, one of statins, on the catecholamine (CA) secretion from the perfused model of the isolated rat adrenal gland, and also to clarify its mechanism of action. DESIGN AND METHOD: The adrenal gland was isolated and perfused with Krebs-bicarbonate. CA was measured directly by using the fluorospectrophotometer. RESULTS: Simvastatin inhibited ACh-evoked CA secretory response in a dose- and time-dependent fashion...